Abstract
B cells in germinal centers (GCs) cycle between light zone (LZ) and dark zone (DZ). The cues in the GC microenvironment that regulate the transition from LZ to DZ have not been well characterized. In Peyer's patches (PPs), transforming growth factor-β (TGFβ) promotes IgA induction in activated B cells that can then differentiate into GC B cells. We show here that TGFβ signaling occurs in B cells in GCs and is distinct from signaling that occurs in activated B cells in PPs. Whereas in activated B cells TGFβ signaling is required for IgA induction, in the GC it was instead required for the transition from LZ to DZ. In the absence of TGFβ signaling, there was an accumulation of LZ GC B cells and reduced antibody affinity maturation likely due to reduced activation of Foxo1. This work identifies TGFβ as a microenvironmental cue that is critical for GC homeostasis and function.
This is a work of the U.S. Government and is not subject to copyright protection in the United States. Foreign copyrights may apply.
Publication types
-
Research Support, N.I.H., Intramural
MeSH terms
-
Animals
-
B-Lymphocytes / immunology*
-
B-Lymphocytes / metabolism
-
Forkhead Box Protein O1 / immunology
-
Forkhead Box Protein O1 / metabolism
-
Germinal Center / cytology
-
Germinal Center / immunology*
-
Germinal Center / metabolism
-
Immunoglobulin A / immunology
-
Immunoglobulin A / metabolism
-
Lymphocyte Activation / immunology
-
Mice, Inbred C57BL
-
Mice, Knockout
-
Mice, Transgenic
-
Peyer's Patches / cytology
-
Peyer's Patches / immunology*
-
Peyer's Patches / metabolism
-
Receptor, Transforming Growth Factor-beta Type I / genetics
-
Receptor, Transforming Growth Factor-beta Type I / immunology
-
Receptor, Transforming Growth Factor-beta Type I / metabolism
-
Receptors, CCR6 / genetics
-
Receptors, CCR6 / immunology
-
Receptors, CCR6 / metabolism
-
Signal Transduction / immunology*
-
Transforming Growth Factor beta / immunology*
-
Transforming Growth Factor beta / metabolism
Substances
-
CCR6 protein, mouse
-
Forkhead Box Protein O1
-
Immunoglobulin A
-
Receptors, CCR6
-
Transforming Growth Factor beta
-
Receptor, Transforming Growth Factor-beta Type I